Intraoperative Strahlentherapie für Brustkrebs - Medizintechnik

Behandlung

Intraoperative Strahlentherapie (IORT) für Brustkrebs

Bei der intraoperativen Strahlentherapie für Brustkrebs wurde in den letzten Jahren ein Weg beschritten, der weg von radikalen Operationsmethoden hin zu einer weniger invasiven, brusterhaltenden Therapie (BET) führte. Ein solcher Wandel zeigt sich nun auch in der Strahlentherapie. Anstelle eines standardisierten Behandlungsplanes wird bei der IORT eine risikoadaptierte Therapie vorgenommen, die den individuellen Risikofaktoren der Patientinnen besser Rechnung trägt und deutlich mehr Behandlungskomfort bietet.

Anders als bei der externen Bestrahlung wird mit dem INTRABEAM^®von ZEISS das Tumorbett gezielt bestrahlt und umliegendes gesundes Gewebe geschont. Bei der IORT für Brustkrebs erfolgt sofort nach der Tumorresektion noch während der Operation eine zirka 30 minütige Bestrahlung. Dadurch wird die herkömmliche, circa sechs Wochen dauernde Nachbestrahlung verkürzt oder kann bei ausgewählten Patientinnen mit niedrigem Risikoprofil sogar ganz entfallen.^1,2

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Intraoperative Strahlentherapie für Brustkrebs TARGIT vs EBRT

Strahlentherapien – risikoadaptierte Alternativen nach brusterhaltender Behandlung

TARGIT Boost Bestrahlung

TARGIT Einmalbestrahlung

Behandlungsschritte

Intraoperative Strahlentherapie für Brustkrebs 1

Schritt 1 Die Position des Tumors wird ermittelt.

Intraoperative Strahlentherapie für Brustkrebs 2

Schritt 2 Während der Operation wird ein minimal invasiver Zugangspunkt geschaffen.

Intraoperative Strahlentherapie für Brustkrebs 3

Schritt 3 Der Tumor wird operativ entfernt.

Intraoperative Strahlentherapie für Brustkrebs 4

Schritt 4 Der passende Applikator (Ø) wird bestimmt und in der Tumorhöhle platziert.

Intraoperative Strahlentherapie für Brustkrebs 5

Schritt 5 Das Tumorbett wird für ca. 30 Minuten lokal bestrahlt.

Intraoperative Strahlentherapie für Brustkrebs 6

Schritt 6 Der Applikator wird entfernt und die Wunde wird geschlossen.

TARGIT-A

The TARGIT-A Trial: „Risk-adapted targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial.“ ¹

_{Jayant S Vaidya, Frederik Wenz, Max Bulsara, Jeffrey S Tobias, David J Joseph, Mohammed Keshtgar, Henrik L Flyger, Samuele Massarut, Michael Alvarado, Christobel Saunders, Wolfgang Eiermann, Marinos Metaxas, Elena Sperk, Marc Sütterlin, Douglas Brown, Laura Esserman, Mario Roncadin, Alastair Thompson, John A Dewar, Helle M R Holtveg, Steffi Pigorsch, Mary Falzon, Eleanor Harris, April Matthews, Chris Brew-Graves, Ingrid Potyka, Tammy Corica, Norman R Williams, Michael Baum, on behalf of the TARGIT trialists’ group.}

Die TARGIT-A Studienergebnisse zeigen, dass diese Methode der konventionellen externen Bestrahlung (EBRT) beim invasiv-duktalen Mammakarzinom nicht unterlegen ist. Nach einem Follow-up von 5 Jahren konnte kein statistisch
signifikanter Unterschied zwischen der Lokalrezidivrate (primärer Endpunkt) bei der EBRT und TARGIT festgestellt werden. Für die Patientinnen bietet die TARGIT Einmalbestrahlung entscheidende Vorteile: durch die einmalige, zielgerichtete
Bestrahlung direkt im Tumorbett kann die Behandlungsdauer auf ca. 30 Minuten verkürzt werden.

Podcast von „The Lancet“ über die 5-Jahresergebnisse der Targit-A Studie

Studiendesign

Intraoperative Strahlentherapie für Brustkrebs Weltkarte Thumbnail

Studien Design

Die TARGIT-A Studie ist momentan die größte multizentrische, randomisierte klinische Studie im Bereich der verkürzten Teilbrustbestrahlung (APBI). In 33 Zentren aus 11 Ländern wurde bei 3451 Patientinnen mit günstiger Prognose die gezielte intraoperative Strahlentherapie (TARGIT) durchgeführt.

Intraoperative Strahlentherapie für Brustkrebs Patienten Thumbnail

Patienten Charakteristika

Für die TARGIT-A Studie wurden Patientinnen mit günstigem Risikoprofil ausgewählt, jedoch nicht ausschließlich ältere. Außerdem gab es auch eine erhebliche Anzahl von Patientinnen mit negativer Prognose.

Zusammenfassung der Ergebnisse

Intraoperative Strahlentherapie für Brustkrebs TARGIT EBRT Thumbnail

Effektivität von TARGIT im Vergleich zu EBRT

Die Ergebnisse zum ipsilateralen Rezidiv zeigen, dass es bei Patientinnen nach 5 Jahren keinen signifikanten Unterschied zwischen der TARGIT Behandlung während der Lumpektomie-OP und der EBRT Behandlung gibt.

mehr

Intraoperative Strahlentherapie für Brustkrebs TAGRIT EBRT Mortalität Thumbnail

Nicht-Brustkrebs Todesfälle

Im Studienarm, bei dem die TARGIT Behandlung während der Lumpektomie-OP durchgeführt wurde, gab es im Vergleich zu EBRT signifikant weniger Todesfälle, welche nicht durch Brustkrebs verursacht wurden, sondern kardiovaskulär oder durch andere Krebsarten bedingt waren.

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Intraoperative Strahlentherapie für Brustkrebs TARGIT EBRT Haut Thumbnail

Grad 3 oder 4 Hautkomplikationen

Wundkomplikationen waren in beiden Gruppen ähnlich. Im Vergleich zur EBRT konnten jedoch Grad 3 oder 4 Hautkomplikationen durch TARGIT signifikant reduziert werden.

6 Monate nach der Randomisierung konnten keine signifikanten Unterschiede zwischen den Wundkomplikationen (sekundärer Endpunkt) bei EBRT und TARGIT festgestellt werden.

n = 3451	TARGIT	EBRT
Wundkomplikationen
Hämatom / Serom, welches mehr als 3 Aspirationen oder operativen Eingriff erfordert	4	2
Wundinfektion, welche intravenöse Antibiose oder operative Intervention erfordert	12	9
Hautschäden / verzögerte Wundheilung	3	5
Total	19 (1.1%)	16 (0.9%)
	p = 0.599
Strahleninduzierte Komplikationen
Strahleninduzierte Grad 3 oder 4 Hautkomplikation gemäß der Radiaton Therapy Oncology Group (RTOG)	4 (0.2%)	13 (0.8%)
	p = 0.029

mehr

Studienfazit

Die randomisierte, multizentrische klinische Studie belegt, dass die gezielte intraoperative Radiotherapie (TARGIT) mit dem INTRABEAM^® von ZEISS der externen Bestrahlung (EBRT) nicht unterlegen ist.

“The most important benefit of TARGIT for a woman with breast cancer is that it allows her to complete her entire local treatment at the time of her operation, with lower toxicity to the breast, the heart and other organs. Our research supports the use of TARGIT concurrent with lumpectomy, provided patients are selected carefully, and should allow patients and their clinicians to make a more informed choice about individualizing their treatment, saving time, money, breasts, and lives.”

_{Professor Jayant Vaidya (FRCS MD, PhD)³

Clinical Trials Group, Division of

Surgery and Interventional

Science, University College

London, London, UK}

Intraoperative Strahlentherapie für Brustkrebs 5-Jahres Resultate Thumbnail

Literatur

Literatur: Themenüberblick

1. Hirntumore

Neuste Literatur

Cifarelli, C. P., Vargo, J. A., Hack, J., Renz, P. B., Poplawski, L., Jacobson, G. M., … Giordano, F. A. (2019). Intraoperative radiotherapy (IORT) for surgically resected brain metastases: Local control and dosimetric analysis. Journal of Global Oncology, 5(suppl 1), 114.

Cifarelli, C. P., Brehmer, S., Vargo, J. A., Hack, J. D., Kahl, K. H., Sarria-Vargas, G., & Giordano, F. A. (2019). Intraoperative radiotherapy (IORT) for surgically resected brain metastases: outcome analysis of an international cooperative study. Journal of Neuro-Oncology, 145(2), 391–397.

Giordano, F. A., Wenz, F., & Petrecca, K. (2016). Rationale for intraoperative radiotherapy in glioblastoma. Journal of Neurosurgical Sciences, 60(3), 350–6.

Giordano, F. A., Brehmer, S., Mürle, B., Welzel, G., Sperk, E., Keller, A., … Wenz, F. (2018). Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial. Neurosurgery.

Sarria, G. R., Sperk, E., Xiaodi, H., Sarria, G. J., Wenz, F., Brehmer, S., … Giordano, F. A. (2019). Intraoperative Radiotherapy for Glioblastoma: An International Pooled Analysis. International Journal of Radiation Oncology*Biology*Physics, 105(1), E107–E108.

Vargo, J. A., Sparks, K. M., Singh, R., Jacobson, G. M., Hack, J. D., & Cifarelli, C. P. (2018). Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery. Journal of Neuro-Oncology, 140(2), 413–420.

Zusätzliche Literatur

Brehmer, S., Guthier, C. V, Clausen, S., Schneider, F., Schulte, D. M., Benker, M., … Giordano, F. A. (2016). Combined stereotactic biopsy and stepping-source interstitial irradiation of unresectable glioblastoma multiforme. Journal of Neurosurgical Sciences.

Giordano, F. A., Brehmer, S., Muerle, B., Welzel, G., Sperk, E., Schneider, F., … Wenz, F. (2016). Initial Results of a Phase 1/2 Trial on Intraoperative Radiation Therapy (IORT) in Newly Diagnosed Glioblastoma Multiforme (INTRAGO). International Journal of Radiation Oncology, Biology, Physics, 96(2S), E67–E68.

Giordano, F. A., Wenz, F., & Petrecca, K. (2016). Rationale for intraoperative radiotherapy in glioblastoma. Journal of Neurosurgical Sciences, 60(3), 350–6.

Giordano, F. A., Abo-Madyan, Y., Brehmer, S., Herskind, C., Sperk, E., Schneider, F., … Wenz, F. (2014). Intraoperative radiotherapy (IORT)-a resurrected option for treating glioblastoma? Translational Cancer Research, 3(1), 94–105.

Han, X., Fu, B., Wu, M., Zhang, H., Li, D., Zhang, J., … Sun, S. (2014). Intraoperative Radiotherapy with INTRABEAM in primary brain tumors after resection: Preliminary reports of 26 cases. Neuro-Oncology, 16.

Kalapurakal, J. A., Goldman, S., Stellpflug, W., Curran, J., Sathiaseelan, V., Marymont, M. H., & Tomita, T. (2006). Phase I study of intraoperative radiotherapy with photon radiosurgery system in children with recurrent brain tumors: Preliminary report of first dose level (10 Gy). International Journal of Radiation Oncology Biology Physics, 65(3), 800–808.

Weil, R. J., Mavinkurve, G. G., Chao, S. T., Vogelbaum, M. a, Suh, J. H., Kolar, M., & Toms, S. a. (2015). Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: initial experience and long-term outcomes. Journal of Neurosurgery, 122(4), 825–832.

2. Brustkrebs

Alvarado, M. D., Mohan, A. J., Esserman, L. J., Park, C. C., Harrison, B. L., Howe, R. J., … Ozanne, E. M. (2013). Cost-effectiveness analysis of intraoperative radiation therapy for early-stage breast cancer. Annals of Surgical Oncology, 20(9), 2873–80.

Harris, E. E. R., & Small, W. (2017). Intraoperative Radiotherapy for Breast Cancer. Frontiers in Oncology, 7(December), 1–8.

Holmes, D. R. (2015). Intraoperative Radiotherapy of the Breast for Early-Stage Breast Cancer: Ready for Primetime. The Breast Journal, 21(2), 181–184.

Holmes, D. R. (2017). Early complications after intraoperative radiotherapy revisited. Journal of Surgical Oncology, 115(7), 779–781.

Keshtgar, M. R. S., Vaidya, J. S., Tobias, J. S., Wenz, F., Joseph, D., Stacey, C., … Baum, M. (2011). Targeted Intraoperative Radiotherapy for Breast Cancer in Patients in Whom External Beam Radiation Is Not Possible. International Journal of Radiation Oncology*Biology*Physics, 80(1), 31–38.

Keshtgar, M. R. S., Williams, N. R., Bulsara, M., Saunders, C., Flyger, H., Cardoso, J. S., … Joseph, D. J. (2013). Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: results from a randomised controlled trial. Breast Cancer Research and Treatment, 140(3), 519–525.

Kolberg, H.-C., Loevey, G., Akpolat-Basci, L., Stephanou, M., Fasching, P. A., Untch, M., … Vaidya, J. S. (2017). Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy. Strahlentherapie Und Onkologie, 193(1), 62–69.

Kolberg, H.-C., Lövey, G., Akpolat-Basci, L., Stephanou, M., Fasching, P., Untch, M., Hoffmann, O., Bulsara, M., Vaidya, J., & Liedtke, C. (2017). Targeted Intraoperative Radiotherapy Tumour Bed Boost during Breast-Conserving Surgery after Neoadjuvant Chemotherapy - a Subgroup Analysis of Hormone Receptor-Positive HER2-Negative Breast Cancer. Breast Care, 12(5), 318–323.

Malter, W., Kirn, V., Richters, L., Fridrich, C., Markiefka, B., Bongartz, R., … Kraemer, S. (2014). Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery: Overview and Single Center Experiences. International Journal of Breast Cancer, 1–6.

Picot, J., Copley, V., Colquitt, J. L., Kalita, N., Hartwell, D., Bryant, J. (2015). The INTRABEAM® photon radiotherapy system for the adjuvant treatment of early breast cancer: A systematic review and economic evaluation. Health Technology Assessment, 19(69), 1–190.

Rivera, R., Banks, A., Casillas-Lopez, A., Rashtian, A., Lewinsky, B., Sheth, P., … Holmes, D. R. (2016). Targeted Intraoperative Radiotherapy for the Management of Ductal Carcinoma In Situ of the Breast. The Breast Journal, 22(1), 63–74.

Sedlmayer, F., Reitsamer, R., Wenz, F., Sperk, E., Fussl, C., Kaiser, J., … Fastner, G. (2017). Intraoperative radiotherapy (IORT) as boost in breast cancer. Radiation Oncology, 12(1), 23.

Sperk, E., Welzel, G., Keller, A., Kraus-Tiefenbacher, U., Gerhardt, A., Sütterlin, M., Wenz, F. (2012). Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomised phase III trial TARGIT A. Breast Cancer Research and Treatment, 135(1), 253–260.

Sperk, E., Astor, D., Keller, A., Welzel, G., Gerhardt, A., Tuschy, B., … Wenz, F. (2014). A cohort analysis to identify eligible patients for intraoperative radiotherapy (IORT) of early breast cancer. Radiation Oncology, 9(1), 154.

Sperk, E. (2019). First per Protocol Analysis of the Prospective Phase II Study of Intraoperative Radiotherapy (IORT) in Elderly Patients with Small Breast Cancer: Targit E(lderly). International Journal of Radiation Oncology*Biology*Physics, 105(1), S8.

Tallet, A., Racadot, S., Boher, J.-M., Cohen, M., Barrou, J., Houvenaeghel, G., Gutowski, M., Delmond, L., & Lemanski, C. (2020). The actual benefit of intraoperative radiation therapy using 50 kV x-rays in early breast cancer: A retrospective study of 676 patients. The Breast Journal.

Vaidya, J. S., Wenz, F., Bulsara, M., Tobias, J. S., Joseph, D. J., Keshtgar, M., … Baum, M. (2014). Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. The Lancet, 383(9917), 603–613.

Vaidya, J. S., Bulsara, M., Wenz, F., Joseph, D., Saunders, C., Massarut, S., … Baum, M. (2015). Pride, prejudice, or science: Attitudes towards the results of the TARGIT-A trial of targeted intraoperative radiation therapy for breast cancer. International Journal of Radiation Oncology Biology Physics, 92(3), 491–497.

Vaidya, J. S., Bulsara, M., Wenz, F., Coombs, N., Singer, J., Ebbs, S., … Baum, M. (2016). Reduced mortality with partial breast irradiation for early breast cancer – a meta-analysis of randomised trials. International Journal of Radiation Oncology*Biology*Physics, 1–7.

Vaidya, J. S., Bulsara, M., Baum, M., Wenz, F., Massarut, S., Pigorsch, S., Alvarado, M., Douek, M., Saunders, C., Flyger, H. L., Eiermann, W., Brew-Graves, C., Williams, N. R., Potyka, I., Roberts, N., Bernstein, M., Brown, D., Sperk, E., Laws, S., … Tobias, J. S. (2020). Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial. BMJ, 370, m2836.

Vaidya, J. S., Bulsara, M., Baum, M., Tobias, J. S., Wenz, F., Massarut, S., Pigorsch, S., Alvarado, M., Douek, M., Saunders, C., Flyger, H. L., Eiermann, W., Brew-Graves, C., Williams, N. R., Potyka, I., Roberts, N., Bernstein, M., Brown, D., Sperk, E., … Joseph, D. J. (2021). Single-dose intraoperative radiotherapy during lumpectomy for breast cancer: an innovative patient-centred treatment. British Journal of Cancer, December 2020, 1–6.

3. Gastrointestinale Tumore

Guo, S., Reddy, C. A., Kolar, M., Woody, N., Mahadevan, A., Deibel, F., … Suh, J. H. (2012). Intraoperative radiation therapy with the photon radiosurgery system in locally advanced and recurrent rectal cancer: retrospective review of the Cleveland clinic experience. Radiation Oncology, 7(1), 110.

Kim, J. W., Cho, Y., Kim, H. S., Choi, W. H., Park, J. S., & Lee, I. J. (2019). A phase II study of intraoperative radiotherapy using a low-energy x-ray source for resectable pancreatic cancer: a study protocol. BMC Surgery, 19(1), 31.

Ma, L., Qiang, J., Yin, H., Lin, L., Jiao, Y., Ma, C., Li, X., Dong, L., Cui, J., Wei, D., Sharma, A. M., Schwartz, D. L., Gu, W., & Chen, H. (2020). Low-kilovolt x-ray intraoperative radiotherapy for pT3 locally advanced colon cancer: a single-institution retrospective analysis. World Journal of Surgical Oncology, 18(1), 132.

Polkowski, W. P., Skórzewska, M. (2014). Intraoperative Radiotherapy with Low-Energy Photons in Rectal Cancer Recurrence. (M. Keshtgar, K. Pigott, & F. Wenz, Eds.), Targeted Intraoperative Radiotherapy in Oncology. Berlin, Heidelberg: Springer Berlin Heidelberg.

Potemin, S., Uvarov, I., Vasilenko, I. (2015). Intraoperative radiotherapy in locally-advanced and recurrent rectal cancer: retrospective review of 68 cases. Transl Cancer Res, 4(2), 189–195.

Potemin, S., Kübler, J., Uvarov, I., Wenz, F., & Giordano, F. (2020). Intraoperative radiotherapy as an immediate adjuvant treatment of rectal cancer due to limited access to external-beam radiotherapy. Radiation Oncology, 15(1), 1–7.

Skórzewska, M., Mielko, J., Kurylcio, A., Romanek, J., Polkowski, W. P. (2016). Intraoperative radiotherapy with low energy photons in recurrent colorectal cancer: a single centre retrospective study. Współczesna Onkologia, 20(1), 52–57.

Susko, M., Lee, J., Salama, J., Thomas, S., Uronis, H., Hsu, D., … Palta, M. (2016). The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer. Annals of Surgical Oncology.

Xue, W., Wang, S., Zhao, Z., Li, Y., Shang, A., Li, D., Yang, J., Wang, T., & Wang, M. (2020). Short-term outcomes of laparoscopic intersphincteric resection with intraoperative radiotherapy using low-energy X-rays for primary locally advanced low rectal cancer: A single center experience. World Journal of Surgical Oncology, 18(1), 1–8.

4. Kopf- und Halstumore

De Felice, F., Musio, D., Tombolini, V. (2016). Intraoperative radiation therapy (IORT) in recurrent head and neck cancer. Oral Oncology, 55(March), e1.

Kyrgias, G., Hajiioannou, J., Tolia, M., Kouloulias, V., Lachanas, V., Skoulakis, C., … Bizakis, I. (2016). Intraoperative radiation therapy (IORT) in head and neck cancer: A systematic review. Medicine, 95(50), e5035.

Münter, M. W., Köppen, U., Ramuscak, A., Sittel, C., Wegner, N. (2015). Intraoperative radiotherapy (IORT) in the treatment of head and neck cancer. Transl Cancer Res, 4(2), 178–181.

Roopashri, G., Baig, M. (2013). Current advances in radiotherapy of head and neck malignancies. Journal of International Oral Health, 5(6), 119–23.

5. Weichteil-Sarkome & nicht-melanozytärer Hautkrebs

Bodner, W. R., Hilaris, B. S., Alagheband, M., Safai, B., Mastoras, C. A., Saraf, S. (2003). Use of low-energy X-rays in the treatment of superficial nonmelanomatous skin cancers. Cancer Investigation, 21(3), 355–362.

Cognetta, A. B., Howard, B. M., Heaton, H. P., Stoddard, E. R., Hong, H. G., Green, W. H. (2012). Superficial x-ray in the treatment of basal and squamous cell carcinomas: a viable option in select patients. Journal of the American Academy of Dermatology, 67(6), 1235–41.

Sarria, G. R., Petrova, V., Abo-Madyan, Y., Wenz, F., Hohenberger, P., Sperk, E., & Giordano, F. A. (2019). Intraoperative Radiotherapy with Low Energy x-Rays for Primary and Recurrent Soft-Tissue Sarcoma. International Journal of Radiation Oncology*Biology*Physics, 105(1), E810.

Tward, J.D., Anker, C, J,. Gaffney, D.K., Bowen, G. . (2012). Radiation Therapy and Skin Cancer. Modern Practices in Radiation Therapy, 207–246.

6. Wirbelsäulenmetastasen

Bludau, F., Reis, T., Schneider, F., Clausen, S., Wenz, F., Obertacke, U. (2015). Kyphoplastie kombiniert mit intraoperativer Radiotherapie (Kypho-IORT). Der Radiologe, 55(10), 859–867.

Bludau, F., Welzel, G., Reis, T., Schneider, F., Sperk, E., Neumaier, C., Ehmann, M., Clausen, S., Obertacke, U., Wenz, F., & Giordano, F. A. (2018). Phase I/II trial of combined kyphoplasty and intraoperative radiotherapy in spinal metastases. The Spine Journal, 18(5), 776–781.

Bludau, F., Welzel, G., Reis, T., Abo-Madyan, Y., Sperk, E., Schneider, F., Clausen, S., Ruder, A. M., Obertacke, U., Ghaly, M. M., Wenz, F., & Giordano, F. A. (2019). Combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) versus external beam radiotherapy (EBRT) for painful vertebral metastases - a randomized phase III study. BMC Cancer, 19(1), 430.

Kayser, R., Ender, S. A., Asse, E., Wilhelm, E., Adler, F., Schmidt, R., … Bludau, F. (2013). Kyphoplastie in Kombination mit intraoperativer Radiotherapie. Der Orthopäde, 42(9), 765–771.

Miglierini, P., Dam-Hieu, P., Key, S. (2014). Kypho-IORT: the first French treatment. Translational Cancer Research, 3(1).

Mohme, M., Riethdorf, S., Dreimann, M., Werner, S., Maire, C. L., Joosse, S. A., Bludau, F., Mueller, V., Neves, R. P. L., Stoecklein, N. H., Lamszus, K., Westphal, M., Pantel, K., Wikman, H., & Eicker, S. O. (2017). Circulating Tumour Cell Release after Cement Augmentation of Vertebral Metastases. Nature Scientific Reports, 7(1), 7196.

Schmidt, R., Wenz, F., Reis, T., Janik, K., Bludau, F., Obertacke, U. (2012). Kyphoplasty and intra-operative radiotheray, combination of kyphoplasty and intra-operative radiation for spinal metastases: technical feasibility of a novel approach. International Orthopaedics, 36(6), 1255–1260.

7. Medizinische Physik

Culberson, W. S., Davis, S. D., Gwe‐Ya Kim, G., Lowenstein, J. R., Ouhib, Z., Popovic, M., Waldron, T. J., Safigholi, H., Simiele, S. J., & Rivard, M. J. (2020). Dose‐rate considerations for the INTRABEAM electronic brachytherapy system: Report from the American association of physicists in medicine task group no. 292. Medical Physics, 47(8).

Eaton, D. J., Gonzalez, R., Duck, S., Keshtgar, M. (2011). Radiation protection for an intra-operative X-ray device. The British Journal of Radiology, 84(1007), 1034–1039.

Eaton, D. J. (2012). Quality assurance and independent dosimetry for an intraoperative x-ray device. Medical Physics, 39(11), 6908.

Goubert, M., Parent, L. (2015). Dosimetric characterization of INTRABEAM® miniature accelerator flat and surface applicators for dermatologic applications. Physica Medica, 31(3), 224–232.

Herskind, C., Griebel, J., Kraus-Tiefenbacher, U., & Wenz, F. (2008). Sphere of Equivalence-A Novel Target Volume Concept for Intraoperative Radiotherapy Using Low-Energy X Rays. International Journal of Radiation Oncology Biology Physics, 72(5), 1575–1581.

Shaikh, M. Y., Burmeister, J., Scott, R., Kumaraswamy, L. K., Nalichowski, A., & Joiner, M. C. (2020). Dosimetric evaluation of incorporating the revised V4.0 calibration protocol for breast intraoperative radiotherapy with the INTRABEAM system. Journal of Applied Clinical Medical Physics, 21(2), 50–59.

Sethi, A., Emami, B., Small, W., & Thomas, T. O. (2018). Intraoperative Radiotherapy With INTRABEAM: Technical and Dosimetric Considerations. Frontiers in Oncology, 8(March), 1–10.

Schneider, F., Clausen, S., Jahnke, A., Steil, V., Bludau, F., Sütterlin, M., … Wenz, F. (2014). Radiation protection for an intraoperative X-ray source compared to C-arm fluoroscopy. Zeitschrift Fur Medizinische Physik, 24(3), 243–251.

Schneider, F., Clausen, S., Thölking, J., Wenz, F., Abo-Madyan, Y. (2014). A novel approach for superficial intraoperative radiotherapy (IORT) using a 50 kV X-ray source: a technical and case report. Journal of Applied Clinical Medical Physics / American College of Medical Physics, 15(1), 4502.

Sethi, A., Chinsky, B., Gros, S., Diak, A. (2015). Tissue inhomogeneity corrections in low-kV intra-operative radiotherapy (IORT). Translational Cancer Research, 4(2), 182–188.

Schneider, F., Greineck, F., Clausen, S., Mai, S., Obertacke, U., Reis, T., & Wenz, F. (2011). Development of a Novel Method for Intraoperative Radiotherapy During Kyphoplasty for Spinal Metastases (Kypho-IORT). International Journal of Radiation Oncology*Biology*Physics, 81(4), 1114–1119.

8. Radiobiologie

Belletti, B., Vaidya, J. S., D’Andrea, S., Entschladen, F., Roncadin, M., Lovat, F., … Massarut, S. (2008). Targeted Intraoperative Radiotherapy Impairs the Stimulation of Breast Cancer Cell Proliferation and Invasion Caused by Surgical Wounding. Clinical Cancer Research, 14(5), 1325–1332.

Emami, B., Woloschak, G., Small Jr, W. (2015). Beyond the linear quadratic model : intraoperative radiotherapy and normal tissue tolerance. Transl Cancer Res, 4(2), 140–147.

Herskind, C., Ma, L., Liu, Q., Zhang, B., Schneider, F., Veldwijk, M. R., & Wenz, F. (2017). Biology of high single doses of IORT: RBE, 5 R’s, and other biological aspects. Radiation Oncology (London, England), 12(1), 24.

Herskind, C., Wenz, F. (2014). Radiobiological aspects of intraoperative tumour-bed irradiation with low-energy X-rays ( LEX-IORT ). Transl Cancer Res, 3(1), 3–17.

Keshtgar, M. R. S., Williams, N. R., Bulsara, M., Saunders, C., Flyger, H., Cardoso, J. S., … Joseph, D. J. (2013). Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: results from a randomised controlled trial. Breast Cancer Research and Treatment, 140(3), 519–525.

Kulcenty, K., Piotrowski, I., Rucinski, M., Wroblewska, J. P., Jopek, K., Murawa, D., & Suchorska, W. M. (2020). Surgical Wound Fluids from Patients with Breast Cancer Reveal Similarities in the Biological Response Induced by Intraoperative Radiation Therapy and the Radiation-Induced Bystander Effect-Transcriptomic Approach. International Journal of Molecular Sciences, 21(3).

Liu, Q., Schneider, F., Ma, L., Wenz, F., Herskind, C. (2013). Relative Biologic Effectiveness (RBE) of 50 kV X-rays Measured in a Phantom for Intraoperative Tumor-Bed Irradiation. International Journal of Radiation Oncology*Biology*Physics, 85(4), 1127–1133.

Minafra, L., & Bravatà, V. (2014). Cell and molecular response to IORT treatment. Translational Cancer Research, 3(1), 32–47.

Sologuren, I., Rodríguez-gallego, C., & Lara, P. C. (2014). Immune effects of high dose radiation treatment: implications of ionizing radiation on the development of bystander and abscopal effects. Transl Cancer Res, 3(1), 18–31.

Wang, M., Maier, P., Wenz, F., Giordano, F. A., & Herskind, C. (2013). Mitogenic signalling in the absence of epidermal growth factor receptor activation in a human glioblastoma cell line. Journal of Neuro-Oncology, 115(3), 323–331.

9. Lebensqualität & kosmetische Ergebnisse

Alvarado, M. D., Conolly, J., Park, C., Sakata, T., Mohan, A. J., Harrison, B. L., … Ozanne, E. M. (2014). Patient preferences regarding intraoperative versus external beam radiotherapy following breast-conserving surgery. Breast Cancer Research and Treatment, 143(1), 135–140.

Andersen, K. G., Gärtner, R., Kroman, N., Flyger, H., Kehlet, H. (2012). Persistent pain after targeted intraoperative radiotherapy (TARGIT) or external breast radiotherapy for breast cancer: A randomised trial. The Breast, 21(1), 46–49.

Corica, T., Nowak, A. K., Saunders, C. M., Bulsara, M., Taylor, M., Vaidya, J. S., … Joseph, D. J. (2016). Cosmesis and breast-related quality of life outcomes following intra-operative radiotherapy for early breast cancer - a sub-study of the TARGIT-A trial. International Journal of Radiation Oncology*Biology*Physics.

Corica, T., Nowak, A. K., Saunders, C. M., Bulsara, M. K., Taylor, M., Williams, N. R., Keshtgar, M., Joseph, D. J., & Vaidya, J. S. (2018). Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A Trial. Radiation Oncology, 13(1), 68.

Corica, T., Saunders, C. M., Bulsara, M. K., Taylor, M., Joseph, D. J., & Nowak, A. K. (2019). Patient preferences for adjuvant radiotherapy in early breast cancer are strongly influenced by treatment received through random assignment. European Journal of Cancer Care, March 2018, e12985.

Coombs, N. J., Coombs, J. M., Vaidya, U. J., Singer, J., Bulsara, M., Tobias, J. S., … Vaidya, J. S. (2016). Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer: data from UK TARGIT-A trial centres and two UK NHS hospitals offering TARGIT IORT. BMJ Open, 6(5).

Darby, S. C., Ewertz, M., McGale, P., Bennet, A. M., Blom-Goldman, U., Brønnum, D., … Hall, P. (2013). Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. New England Journal of Medicine, 368(11), 987–998

Elsberger, B., Romsauerova, A., Vinnicombe, S., Whelehan, P., Brown, D. C., Dewar, J. A., … Evans, A. (2014). Comparison of mammographic findings after intraoperative radiotherapy or external beam whole breast radiotherapy. European Journal of Surgical Oncology, 40(2), 163–167.

Holmes, D. R., & Zimmerman, R. (2017). Intraoperative radiotherapy: Patient selection, management, and follow-up. Journal of Surgical Oncology, 116(7), 824–830.

Keshtgar, M. R. S., Williams, N. R., Bulsara, M., Saunders, C., Flyger, H., Cardoso, J. S., … Joseph, D. J. (2013). Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: results from a randomised controlled trial. Breast Cancer Research and Treatment, 140(3), 519–525.

Malter, W., Kirn, V., Mallmann, P., & Kraemer, S. (2014). Oncoplastic breast reconstruction after IORT. Translational Cancer Research, 3(1), 74–82.

Welzel, G., Boch, A., Sperk, E., Hofmann, F., Kraus-Tiefenbacher, U., Gerhardt, A., … Wenz, F. (2013). Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomised phase III trial TARGIT-A. Radiation Oncology, 8(1), 9.

Williams, N., Kurylcio, A., Jankiewicz, M., Romanek, J., Polkowski, W., Michalopoulos, N., & Keshtgar, M. (2017). Cosmetic outcome after breast conserving surgery and either external beam or intraoperative radiotherapy for early breast cancer: Objective assessment of patients from a randomized controlled trial in Lublin, Poland. European Journal of Cancer, 6, 867–870.

10. Intraoperative Strahlentherapie (IORT)

Eaton, D. J. (2015). Electronic brachytherapy—current status and future directions. The British Journal of Radiology, 88(1049), 20150002.

Harris, E. E. R., & Small, W. (2017). Intraoperative Radiotherapy for Breast Cancer. Frontiers in Oncology, 7(December), 1–8.

Holmes, D. R. (2015). Intraoperative Radiotherapy of the Breast for Early-Stage Breast Cancer: Ready for Primetime. The Breast Journal, 21(2), 181–184.

Wenz, F. (2017). Keynote Address at the American Society of Breast Surgeons 18th Annual Meeting. Annals of Surgical Oncology, Aug.

11. Leitlinien & Empfehlungen

Aetna. (2015). Intraoperative Radiation Therapy (IORT).

Cardoso, F., Kyriakides, S., Ohno, S., Penault-Llorca, F., Poortmans, P., Rubio, I. T., Zackrisson, S., & Senkus, E. (2019). Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 374, 1–77.

NHS. (2018). National Institute for Health and Care Excellence Intrabeam - radiotherapy system for adjuvant treatment of early breast cancer. Technology Appraisal Guidance. Retrieved January 31, 2018

NCCN. (2020). NCCN Clinical Practical Guidelines in Oncology - Cancer Type: Breast, Colon, Rectal, H&N...

Niyazi, M., Brada, M., Chalmers, A. J., Combs, S. E., Erridge, S. C., Fiorentino, A., … Belka, C. (2016). ESTRO-ACROP guideline “target delineation of glioblastomas.” Radiotherapy and Oncology, 118(1), 35–42.

Onkologie, L. (2020). Leitlinienprogramm Onkologie: S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.3.

Polgár, C., Limbergen, E. Van, Pötter, R., Kovács, G., Polo, A., Lyczek, J., … Strnad, V. (2010). Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: Recommendations of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group. Radiotherapy and Oncology, 94(3), 264–273.

Smith, B. D., Bellon, J. R., Blitzblau, R., Freedman, G., Haffty, B., Hahn, C., Halberg, F., Hoffman, K., Horst, K., Moran, J., Patton, C., Perlmutter, J., Warren, L., Whelan, T., Wright, J. L., & Jagsi, R. (2018). Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Practical Radiation Oncology, 8(3), 145–152.

Tsao, M. N., Rades, D., Wirth, A., Lo, S. S., Danielson, B. L., Gaspar, L. E., Sperduto, P. W., Vogelbaum, M. A., Radawski, J. D., Wang, J. Z., Gillin, M. T., Mohideen, N., Hahn, C. A., & Chang, E. L. (2012). Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline. Practical Radiation Oncology, 2(3), 210–225.

Vaidya, J. S., Wenz, F., Bulsara, M., Tobias, J. S., Joseph, D. J., Saunders, C., Brew-Graves, C., Potyka, I., Morris, S., Vaidya, H. J., Williams, N. R., & Baum, M. (2016). An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial). Health Technology Assessment, 20(73), 1–188.

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